730 PLASMA SPECTROCHEMISTRY
Plasma-based instrumental techniques that are useful for pharmaceutical analyses fall into two major categories: those based on the inductively coupled plasma, and those where a plasma is generated at or near the surface of the sample. An inductively coupled plasma (ICP) is a high-temperature excitation source that desolvates, vaporizes, and atomizes aerosol samples and ionizes the resulting atoms. The excited analyte ions and atoms can then subsequently be detected by observing their emission lines, a method termed inductively coupled plasmaatomic emission spectroscopy (ICPAES), also known as inductively coupled plasmaoptical emission spectroscopy (ICPOES); or the excited or ground state ions can be determined by a technique known as inductively coupled plasmamass spectrometry (ICPMS). ICPAES and ICPMS may be used for either single- or multi-element analysis, and they provide good general-purpose procedures for either sequential or simultaneous analyses over an extended linear range with good sensitivity.
An emerging technique in plasma spectrochemistry is laser-induced breakdown spectroscopy (LIBS). In LIBS, a solid, liquid, or gaseous sample is heated directly by a pulsed laser, or indirectly by a plasma generated by the laser. As a result, the sample is volatilized at the laser beam contact point, and the volatilized constituents are reduced to atoms, molecular fragments, and larger clusters in the plasma that forms at or just above the surface of the sample. Emission from the atoms and ions in the sample is collected, typically using fiber optics or a remote viewing system, and measured using an array detector such as a charge-coupled device (CCD). LIBS can be used for qualitative analysis or against a working standard curve for quantitative analysis. Although LIBS is not currently in wide use by the pharmaceutical industry, it might be suited for at-line or on-line measurements in a production setting as well as in the laboratory. Because of its potential, it should be considered a viable technique for plasma spectrochemistry in the pharmaceutical laboratory. However, because LIBS is still an emerging technique, details will not be further discussed in this general chapter.1
Sample preparation is critical to the success of plasma-based analysis and is the first step in performing any analysis via ICPAES or ICPMS. Plasma-based techniques are heavily dependent on sample transport into the plasma, and because ICPAES and ICPMS share the same sample introduction system, the means by which samples are prepared may be applicable to either technique. The most conventional means by which samples are introduced into the plasma is via solution nebulization. If solution nebulization is employed, solid samples must be dissolved in order to be presented into the plasma for analysis. Samples may be dissolved in any appropriate solvent. There is a strong preference for the use of aqueous or dilute nitric acid solutions, because there are minimal interferences with these solvents compared to other solvent choices. Hydrogen peroxide, hydrochloric acid, sulfuric acid, perchloric acid, combinations of acids, or various concentrations of acids can all be used to dissolve the sample for analysis. Dilute hydrofluoric acid may also be used, but great care must be taken to ensure the safety of the analyst, as well as to protect the quartz sample introduction equipment when using this acid; specifically, the nebulizer, spray chamber, and inner torch tube should be manufactured from hydrofluoric acid-tolerant materials. Additionally, alternative means of dissolving the sample can be employed. These include, but are not limited to, the use of dilute bases, straight or diluted organic solvents, combinations of acids or bases, and combinations of organic solvents.
When samples are introduced into the plasma via solution nebulization, it is important to consider the potential matrix effects and interferences that might arise from the solvent. The use of an appropriate internal standard and/or matching the standard matrix with samples should be applied for ICPAES and ICPMS analyses in cases where accuracy and precision are not adequate. In either event, the selection of an appropriate internal standard should consider the analyte in question, ionization energy, wavelengths or masses, and the nature of the sample matrix.
Where a sample is found not to be soluble in any acceptable solvent, a variety of digestion techniques can be employed. These include hot-plate digestion and microwave-assisted digestions, including open-vessel and closed-vessel approaches. The decision regarding the type of digestion technique to use depends on the nature of the sample being digested, as well as on the analytes of interest.
Open-vessel digestion is generally not recommended for the analysis of volatile metals, e.g., selenium and mercury. The suitability of a digestion technique, whether open-vessel or closed-vessel, should be supported by spike recovery experiments in order to verify that, within an acceptable tolerance, volatile metals have not been lost during sample preparation. Use acids, bases, and hydrogen peroxide of ultra-high purity, especially when ICPMS is employed. Deionized water must be at least 18 megaohm. Check diluents for interferences before they are used in an analysis. Because it is not always possible to obtain organic solvents that are free of metals, use organic solvents of the highest quality possible with regard to metal contaminants.
It is important to consider the selection of the type, material of construction, pretreatment, and cleaning of analytical labware used in ICPAES and ICPMS analyses. The material must be inert and, depending on the specific application, resistant to caustics, acids, and/or organic solvents. For some analyses, diligence must be exercised to prevent the adsorption of analytes onto the surface of a vessel, particularly in ultra-trace analyses. Contamination of the sample solutions from metal and ions present in the container can also lead to inaccurate results.
The use of labware that is not certified to meet Class A tolerances for volumetric flasks is acceptable if the linearity, accuracy, and precision of the method have been experimentally demonstrated to be suitable for the purpose at hand.
There are two ways to introduce the sample into the nebulizer: by a peristaltic pump and by self-aspiration. The peristaltic pump is preferred and serves to ensure that the flow rate of sample and standard solution to the nebulizer is the same irrespective of sample viscosity. In some cases, where a peristaltic pump is not required, self-aspiration can be used.
A wide variety of nebulizer types is available, including pneumatic (concentric and cross-flow), grid, and ultrasonic nebulizers. Micronebulizers, high-efficiency nebulizers, direct-injection high-efficiency nebulizers, and flow-injection nebulizers are also available. The selection of the nebulizer for a given analysis should consider the sample matrix, analyte, and desired sensitivity. Some nebulizers are better suited for use with viscous solutions or those containing a high concentration of dissolved solids, whereas others are better suited for use with organic solutions.
Note that the self-aspiration of a fluid is due to the Bernoulli, or Venturi, effect. Not all types of nebulizers will support self-aspiration. The use of a concentric nebulizer, for example, is required for self-aspiration of a solution.
Once a sample leaves the nebulizer as an aerosol, it enters the spray chamber, which is designed to permit only the smallest droplets of sample solution into the plasma; as a result, typically only 1% to 2% of the sample aerosol reaches the ICP, although some special-purpose nebulizers have been designed that permit virtually all of the sample aerosol to enter the ICP. As with nebulizers, there is more than one type of spray chamber available for use with ICPAES or ICPMS. Examples include the Scott double-pass spray chamber, as well as cyclonic spray chambers of various configurations. The spray chamber must be compatible with the sample and solvent and must equilibrate and wash out in as short a time as possible. When a spray chamber is selected, the nature of the sample matrix, the nebulizer, the desired sensitivity, and the analyte should all be considered.
Gas and liquid chromatography systems can be interfaced with ICPAES and ICPMS for molecular speciation, ionic speciation, or other modes of separation chemistry, based on elemental emission or mass spectrometry.
Ultimately, the selection of sample introduction hardware should be demonstrated experimentally to provide sufficient specificity, sensitivity, linearity, accuracy, and precision of the analysis at hand.
In addition to solution nebulization, it is possible to analyze solid samples directly via laser ablation (LA). In such instances, the sample enters the torch as a solid aerosol. LAICPAES and LAICPMS are better suited for qualitative analyses of pharmaceutical compounds because of the difficulty in obtaining appropriate standards. Nonetheless, quantitative analyses can be performed if it can be demonstrated through appropriate method validation that the available standards are adequate.2
Single- or multi-element standard solutions, whose concentrations are traceable to primary reference standards, such as those of the National Institute of Standards and Technology (NIST), can be purchased for use in the preparation of working standard solutions. Alternatively, standard solutions of elements can be accurately prepared from standard materials and their concentrations, determined independently, as appropriate. Working standard solutions, especially those used for ultra-trace analyses, may have limited shelf life. As a general rule, working standard solutions should be retained for no more than 24 hours unless stability is demonstrated experimentally. The selection of the standard matrix is of fundamental importance in the preparation of element standard solutions. Spike recovery experiments should be conducted with specific sample matrices in order to determine the accuracy of the method. If sample matrix effects cause excessive inaccuracies, standards, blanks, and sample solutions should be matrix matched, if possible, in order to minimize matrix interferences.
In cases where matrix matching is not possible, an appropriate internal standard or the method of standard additions should be used for ICPAES or ICPMS. Internal standards can also be introduced through a T connector into the sample uptake tubing. In any event, the selection of an appropriate internal standard should consider the analytes in question, their ionization and excitation energies, their chemical behavior, their wavelengths or masses, and the nature of the sample matrix. Ultimately, the selection of an internal standard should be demonstrated experimentally to provide sufficient specificity, sensitivity, linearity, accuracy, and precision of the analysis at hand.
The method of standard additions involves adding a known concentration of the analyte element to the sample at no fewer than two concentration levels plus an unspiked sample preparation. The instrument response is plotted against the concentration of the added analyte element, and a linear regression line is drawn through the data points. The absolute value of the x-intercept multiplied by any dilution factor is the concentration of the analyte in the sample.
The presence of dissolved carbon at concentrations of a small percentage in aqueous solutions enhances ionization of selenium and arsenic in an inductively coupled argon plasma. This phenomenon frequently results in a positive bias for ICPAES and ICPMS selenium and arsenic quantification measurements, which can be remedied by using the method of standard additions or by adding a small percentage of carbon, such as analytically pure glacial acetic acid, to the linearity standards.
The components that make up the ICP excitation source include the argon gas supply, torch, radio frequency (RF) induction coil, impedance-matching unit, and RF generator. Argon gas is almost universally used in an ICP. The plasma torch consists of three concentric tubes designated as the inner, the intermediate, and the outer tube. The intermediate and outer tubes are almost universally made of quartz. The inner tube can be made of quartz or alumina if the analysis is conducted with solutions containing hydrofluoric acid. The nebulizer gas flow carries the aerosol of the sample solution into and through the inner tube of the torch and into the plasma. The intermediate tube carries the intermediate (sometimes referred to as the auxiliary) gas. The intermediate gas flow helps to lift the plasma off the inner and intermediate tubes to prevent their melting and the deposition of carbon and salts on the inner tube. The outer tube carries the outer (sometimes referred to as the plasma or coolant) gas, which is used to form and sustain the toroidal plasma. The tangential flow of the coolant gas through the torch constricts the plasma and prevents the ICP from expanding to fill the outer tube, keeping the torch from melting. An RF induction coil, also called the load coil, surrounds the torch and produces an oscillating magnetic field, which in turn sets up an oscillating current in the ions and electrons produced from the argon. The impedance-matching unit serves to efficiently couple the RF energy from the generator to the load coil. The unit can be of either the active or the passive type. An active matching unit adjusts the impedance of the RF power by means of a capacitive network, whereas the passive type adjusts the impedance directly through the generator circuitry. Within the load coil of the RF generator, the energy transfer between the coil and the argon creates a self-sustaining plasma. Collisions of the ions and electrons liberated from the argon ionize and excite the analyte atoms in the high-temperature plasma. The plasma operates at temperatures of 6,000 to 10,000 K, so most covalent bonds and analyte-to-analyte interactions have been eliminated.
An inductively coupled plasma can use either an optical or a mass spectral detection system. In the former case, ICPAES, analyte detection is achieved at an emission wavelength of the analyte in question. Because of differences in technology, a wide variety of ICPAES systems are available, each with different capabilities, as well as different advantages and disadvantages. Simultaneous-detection systems are capable of analyzing multiple elements at the same time, thereby shortening analysis time and improving background detection and correction. Sequential systems move from one wavelength to the next to perform analyses, and often provide a larger number of analytical lines from which to choose. Array detectors, including charge-coupled devices and charge-injection devices, with detectors on a chip, make it possible to combine the advantages of both simultaneous and sequential systems. These types of detection devices are used in the most powerful spectrometers, providing rapid analysis and a wide selection of analytical lines.
The ICP can be viewed in either axial or radial (also called lateral) mode. The torch is usually positioned horizontally in axially viewed plasmas and is viewed end on, whereas it is positioned vertically in radially viewed plasmas and is viewed from the side. Axial viewing of the plasma can provide higher signal-to-noise ratios (better detection limits and precision); however, it also incurs greater matrix and spectral interferences. Methods validated on an instrument with a radial configuration will probably not be completely transferable to an instrument with an axial configuration, and vice versa.
Additionally, dual-view instrument systems are available, making it possible for the analyst to take advantage of either torch configuration. The selection of the optimal torch configuration will depend on the sample matrix, analyte in question, analytical wavelength(s) used, cost of instrumentation, required sensitivity, and type of instrumentation available in a given laboratory.
Regardless of torch configuration or detector technology, ICPAES is a technique that provides a qualitative and/or quantitative measurement of the optical emission from excited atoms or ions at specific wavelengths. These measurements are then used to determine the analyte concentration in a given sample. Upon excitation, an atom or atomic ion emits an array of different frequencies of light that are characteristic of the distinct energy transition allowed for that element. The intensity of the light is generally proportional to the analyte concentration. It is necessary to correct for the background emission from the plasma. Sample concentration measurements are usually determined from a working curve of known standards over the concentration range of interest. It is, however, also possible to perform a single-point calibration under certain circumstances, such as with limit tests, if the methodology has been validated for sufficient specificity, sensitivity, linearity, accuracy, precision, ruggedness, and robustness.
Because there are distinct transitions between atomic energy levels, and because the atoms in an ICP are rather dilute, emission lines have narrow bandwidths. However, because the emission spectra from the ICP contain many lines, and because wings of these lines overlap to produce a nearly continuous background on top of the continuum that arises from the recombination of argon ions with electrons, a high-resolution spectrometer is required in ICPAES. The decision regarding which spectral line to measure should include an evaluation of potential spectral interferences. All atoms in a sample are excited simultaneously; however, the presence of multiple elements in some samples can lead to spectral overlap. Spectral interference can also be caused by background emission from the sample or plasma. Modern ICPs usually have background correction available, and a number of background correction techniques can be applied. Simple background correction typically involves measuring the background emission intensity at some point away from the main peak and subtracting this value from the total signal being measured. Mathematical modeling to subtract the interfering signal as a background correction can also be performed with certain types of ICPAES spectrometers.
The selection of the analytical spectral line is critical to the success of an ICPAES analysis, regardless of torch configuration or detector type. Though some wavelengths are preferred, the final choice must be made in the context of the sample matrix, the type of instrument being used, and the sensitivity required. Analysts might choose to start with the wavelengths recommended by the manufacturer of their particular instrument and select alternative wavelengths based on manufacturer recommendations or published wavelength tables.3,4,5,6,7 Ultimately, the selection of analytical wavelengths should be demonstrated experimentally to provide sufficient specificity, sensitivity, linearity, accuracy, and precision of the analysis at hand.
Forward power, gas flow rates, viewing height, and torch position can all be optimized to provide the best signal. However, it must also be kept in mind that these same variables can influence matrix and spectral interferences.
In general, it is desirable to operate the ICP under robust conditions, which can be gauged on the basis of the MgII/MgI line pair at (280.270 nm/285.213 nm). If that ratio of intensities is above 6.0 in an aqueous solution, the ICP is said to be robust, and is less susceptible to matrix interferences. A ratio of about 10.0 is generally what is sought. Note that the term robust conditions is unrelated to robustness as applied to analytical method validation. Operation of an instrument with an MgII/MgI ratio greater than 6.0 is not mandated, but is being suggested as a means of optimizing instrument parameters in many circumstances.
The analysis of the Group I elements can be an exception to this strategy. When atomic ions are formed from elements in this group, they assume a noble gas electron configuration, with correspondingly high excitation energy. Because the first excited state of these ions is extremely high, few are excited, so emission intensity is correspondingly low. This situation can be improved by reducing the fractional ionization, which can in turn be achieved by using lower forward power settings in combination with adjusted viewing height or nebulizer gas flow, or by adding an ionization suppression agent to the samples and standards.
When organic solvents are used, it is often necessary to use a higher forward power setting, higher intermediate and outer gas flows, and a lower nebulizer gas flow than would be employed for aqueous solutions, as well as a reduction in the nebulizer gas flow. When using organic solvents, it may also be necessary to bleed small amounts of oxygen into the torch to prevent carbon buildup in the torch.
The wavelength accuracy for ICPAES detection must comply with the manufacturer's applicable operating procedures. Because of the inherent differences among the types of instruments available, there is no general system suitability procedure that can be employed. Calibration routines recommended by the instrument manufacturer for a given ICPAES instrument should be followed. These might include, but are not limited to, use of a multi-element wavelength calibration with a reference solution, internal mercury (Hg) wavelength calibration, and peak search. The analyst should perform system checks in accordance with the manufacturer's recommendations.
The instrument must be standardized for quantification at time of use. However, because ICPAES is a technique generally considered to be linear over a range of 6 to 8 orders of magnitude, it is not always necessary to continually demonstrate linearity by the use of a standard curve composed of multiple standards. Once a method has been developed and is in routine use, it is possible to calibrate with a blank and a single standard. One-point standardizations are suitable for conducting limit tests on production materials and final products if the methodology has been rigorously validated for sufficient specificity, sensitivity, linearity, accuracy, precision, ruggedness, and robustness. The use of a single-point standardization is also acceptable for qualitative ICPAES analyses, where the purpose of the experiment is to confirm the presence or absence of elements without the requirement of an accurate quantification.
An appropriate blank solution and standards that bracket the expected range of the sample concentrations should be assayed and the detector response plotted as a function of analyte concentration, as in the case where the concentration of a known component is being determined within a specified tolerance. However, it is not always possible to employ a bracketing standard when an analysis is performed at or near the detection limit. This lack of use of a bracketing standard is acceptable for analyses conducted to demonstrate the absence or removal of elements below a specified limit. The number and concentrations of standard solutions used should be based on the purpose of the quantification, the analyte in question, the desired sensitivity, and the sample matrix. Regression analysis of the standard plot should be employed to evaluate the linearity of detector response, and individual monographs may set criteria for the residual error of the regression line. Optimally, a correlation coefficient of not less than 0.99, or as indicated in the individual monograph, should be demonstrated for the working curve. Here, too, however, the nature of the sample matrix, the analyte(s), the desired sensitivity, and the type of instrumentation available may dictate a correlation coefficient lower than 0.99. The analyst should use caution when proceeding with such an analysis, and should employ additional working standards.
To demonstrate the stability of the system's initial standardization, a solution used in the initial standard curve must be reassayed as a check standard at appropriate intervals throughout the analysis of the sample set. The reassayed standard should agree with its expected value to within ±10%, or as specified in an individual monograph, for single-element analyses when analytical wavelengths are between 200 and 500 nm, or concentrations are >1 µg per mL. The reassayed standard should agree with its theoretical value to within ±20%, or as specified in an individual monograph, for multi-element analyses, when analytical wavelengths are <200 nm or >500 nm, or at concentrations of <1 µg per mL. In cases where an individual monograph provides different guidance regarding the reassayed check standard, the requirements of the monograph take precedence.
Follow the procedure as directed in the individual monograph for the instrumental parameters. Because of differences in manufacturers' equipment configurations, the manufacturer's suggested default conditions may be used and modified as needed. The specification of definitive parameters in a monograph does not preclude the use of other suitable operating conditions, and adjustments of operating conditions may be necessary. Alternative conditions must be supported by suitable validation data, and the conditions in the monograph will take precedence for official purposes. Data collected from a single sample introduction are treated as a single result. This result might be the average of data collected from replicate sequential readings from a single solution introduction of the appropriate standard or sample solution. Sample concentrations are calculated versus the working curve generated by plotting the detector response versus the concentration of the analyte in the standard solutions. This calculation is often performed directly by the instrument.
When an inductively coupled plasma uses a mass spectral detection system, the technique is referred to as inductively coupled plasmamass spectrometry (ICPMS). In this technique, analytes are detected directly at their atomic masses. Because these masses must be charged to be detected in ICPMS, the method relies on the ability of the plasma source to both atomize and ionize sample constituents. As is the case with ICPAES, a wide variety of ICPMS instrumentation systems are available.
The systems most commonly in use are quadrupole-based systems. Gaining in interest is time-of-flight ICPMS. Although still not in widespread use, this approach may see greater use in the future. Additionally, high-resolution sector field instruments are available.
Regardless of instrument design or configuration, ICPMS provides both a qualitative and a quantitative measurement of the components of the sample. Ions are generated from the analyte atoms by the plasma. The analyte ions are then extracted from the atmospheric-pressure plasma through a sampling cone into a lower-pressure zone, ordinarily held at a pressure near 1 Torr. In this extraction process, the sampled plasma gases, including the analyte species, form a supersonic beam, which dictates many of the properties of the resulting analyte ions. A skimmer cone, located behind the sampling cone, skims the supersonic beam of ions as they emerge from the sampling cone. Behind the skimmer cone is a lower-pressure zone, often held near a milliTorr. Lastly, the skimmed ions pass a third-stage orifice to enter a zone held near a microTorr, where they encounter ion optics and are passed into the mass spectrometer. The mass spectrometer separates the ions according to their mass-to-charge (m/z) ratios. The ICPMS has a mass range up to 240 atomic mass units (amu). Depending on the equipment configuration, analyte adducts can form with diluents, with argon, or with their decomposition products. Also formed are oxides and multiply-charged analyte ions, which can increase the complexity of the resulting mass spectra. Interferences can be minimized by appropriate optimization of operational parameters, including gas flows (central, intermediate, and outer gas flow rates), sample-solution flow, RF power, extraction-lens voltage, etc., or by the use of collision or reaction cells, or cool plasma operation, if available on a given instrument. Unless a laboratory is generating or examining isotopes that do not naturally occur, a list of naturally occurring isotopes will provide the analyst with acceptable isotopes for analytical purposes. Isotopic patterns also serve as an aid to element identification and confirmation. Additionally, tables of commonly found interferences and polyatomic isobaric interferences and correction factors can be used.
ICPMS generally offers considerably lower (better) detection limits than ICPAES, largely because of the extremely low background that it generates. This ability is a major advantage of ICPMS for determination of very low analyte concentrations or when elimination of matrix interferences is required. In the latter case, some interferences can be avoided simply by additional dilution of the sample solution. In some applications, analytes can be detected below the parts per trillion (ppt) level using ICPMS. As a general rule, ICPMS as a technique requires that samples contain significantly less total dissolved solids than does ICPAES.
The selection of the analytical mass to use is critical to the success of an ICPMS analysis, regardless of instrument design. Though some masses are often considered to be the primary ones, because of their high natural abundance, an alternative mass for a given element is often used to avoid spectral overlaps (isobaric interferences). Selection of an analytical mass must always be considered in the context of the sample matrix, the type of instrument being used, and the concentrations to be measured. Analysts might choose to start with masses recommended by the manufacturer of their particular instrument and select alternate masses based on manufacturer's recommendations or published tables of naturally occurring isotopes.8
Optimization of an ICPMS method is also highly dependent on the plasma parameters and means of sample introduction. Forward power, gas flow rates, and torch position may all be optimized to provide the best signal. When organic solvents are used, it is often necessary to use a higher forward power setting and a lower nebulizer flow rate than would be used for aqueous solutions. Additionally, when organic solvents are used, it might be necessary to introduce small amounts of oxygen into the central or intermediate gas to prevent carbon buildup in the torch or on the sampler cone orifice. The use of a platinum-tipped sampling or skimmer cone may also be required in order to reduce cone degradation with some organic solvents.
The mass spectral accuracy for ICPMS detection must be in accordance with the applicable operating procedures. Because of the inherent differences between the types of instruments available, there is no general system suitability procedure that can be employed. Analysts should refer to the tests recommended by the instrument manufacturer for a given ICPMS instrument. These may include, but are not limited to, tuning on a reference mass or masses, peak search, and mass calibration. The analyst should perform system checks recommended by the instrument manufacturer.
The instrument must be standardized for quantification at the time of use. Because the response (signal vs. concentration) of ICPMS is generally considered to be linear over a range of 6 to 8 orders of magnitude, it is not always necessary to continually demonstrate linearity by the use of a working curve. Once a method has been developed and is in routine use, it is common practice to calibrate with a blank and a single standard. One-point standardizations are suitable for conducting limit tests on production materials and final products, provided that the methodology has been rigorously validated for sufficient specificity, sensitivity, linearity, accuracy, precision, ruggedness, and robustness. An appropriate blank solution and standards that bracket the expected range of the sample concentrations should be assayed and the detector response plotted as a function of analyte concentration. The number and concentration of standard solutions used should be based on the analyte in question, the expected concentrations, and the sample matrix, and should be left to the discretion of the analyst. Optimally, a correlation coefficient of not less than 0.99, or as indicated in the individual monograph, should be demonstrated for the working standard curve. Here, too, however, the nature of the sample matrix, the analyte, the desired sensitivity, and the type of instrumentation available might dictate a correlation coefficient lower than 0.99. The analyst should use caution when proceeding with such an analysis and should employ additional working standards.
To demonstrate the stability of the system since initial standardization, a solution used in the initial standard curve must be reassayed as a check standard at appropriate intervals throughout the analysis of the sample set. Appropriate intervals may be established as occurring after every fifth or tenth sample, or as deemed adequate by the analyst, on the basis of the analysis being performed. The reassayed standard should agree with its expected value to within ±10% for single-element analyses when analytical masses are free of interferences and when concentrations are >1 ng per mL. The reassayed standard should agree with its expected value to within ±20% for multi-element analyses, or when concentrations are <1 ng per mL. In cases where an individual monograph provides different guidance regarding the reassayed check standard, the requirements of the monograph take precedence.
The method of standard additions should be employed in situations where matrix interferences are expected or suspected. This method involves adding a known concentration of the analyte element to the sample solution at no fewer than two concentration levels. The instrument response is plotted against the concentration of the added analyte element, and a linear regression line is drawn through the data points. The absolute value of the x-intercept multiplied by any dilution factor is the concentration of the analyte in the sample.
Follow the procedure as directed in the individual monograph for the detection mode and instrument parameters. The specification of definitive parameters in a monograph does not preclude the use of other suitable operating conditions, and adjustments of operating conditions may be necessary. Alternative conditions must be supported by suitable validation data, and the conditions in the monograph will take precedence for official purposes. Because of differences in manufacturers' equipment configurations, the analyst may wish to begin with the manufacturer's suggested default conditions and modify them as needed. Data collected from a single sample introduction are treated as a single result. Data collected from replicate sequential readings from a single introduction of the appropriate standard or sample solutions are averaged as a single result. Sample concentrations are calculated versus the working curve generated by plotting the detector response versus the concentration of the analyte in the standard solutions. With modern instruments, this calculation is often performed by the instrument.
auxiliary gas: See Intermediate (or Auxiliary) Gas.
axial viewing: A configuration of the plasma for AES in which the plasma is directed toward the spectrometer optical path, also called end-on viewing.
central (or nebulizer) gas: One of three argon gas flows in an ICP torch. The central gas is used to help create a fine mist of the sample solution when solution nebulization is employed. This fine mist is then directed through the central tube of the torch and into the plasma.
collision cell: A design feature of some ICPMS instruments. Collision cells are used to reduce interferences from argon species or polyatomic ions and facilitate the analysis of elements that might be affected by those interferences.
cool plasma: Plasma conditions used for ICPMS that result in a plasma that is cooler than that normally used for an analysis. This condition is achieved by using a lower forward power setting and higher central-gas flow rate, and is used to help reduce isotopic interferences caused by argon and some polyatomic ions.
coolant gas: See Outer (or Coolant or Plasma) Gas.
forward power: The number of watts used to ignite and sustain the plasma during an analysis. Forward power requirements may vary, depending on sample matrix and analyte.
intermediate (or auxiliary) gas: Gas used to lift the plasma off the surface of the torch, thereby preventing melting of the intermediate tube and the formation of carbon and salt deposits on the inner tube.
internal standard: An element added to or present in the same concentration in blanks, standards, and samples to act as an intensity reference for the analysis. An internal standard should be used for ICPAES work and must always be used for quantitative ICPMS analyses.
lateral viewing: See Radial Viewing.
m: The ion mass of interest.
multiply-charged ions: Atoms that, when subjected to the high-ionization temperature of the ICP, can form doubly or triply charged ions (X++, X+++, etc.). When detected by MS, the apparent mass of these ions will be ½ or 1/3 that of the atomic mass.
nebulizer: Used to form a consistent sample aerosol that mixes with the argon gas, which is subsequently sent into the ICP.
outer (or coolant or plasma) gas: The main gas supply for the plasma.
plasma gas: See Outer (or Coolant or Plasma) Gas.
radial viewing: A configuration of the plasma for AES in which the plasma is viewed orthogonal to the spectrometer optic path. Also called side-on viewing. See also Lateral Viewing.
reaction cell: Similar to Collision Cell, but operating on a different principle. Designed to reduce or eliminate spectral interferences.
sampling cone: A metal cone (usually nickel-, aluminum-, or platinum-tipped) with a small opening, through which ionized sample material flows after leaving the plasma.
sequential: A type of detector configuration for AES or MS in which discrete emission lines or isotopic peaks are observed by scanning or hopping across the spectral range by means of a monochromator or scanning mass spectrometer.
simultaneous: A type of detector configuration for AES or MS in which all selected emission lines or isotopic peaks are observed at the same time by using a polychromator or simultaneous mass spectrometer, offering increased analysis speed for analyses of multi-element samples.
skimmer cone: A metal cone through which ionized sample flows after leaving the sampling cone and before entering the high-vacuum region of an ICPMS.
standard additions: A method used to determine the actual analyte concentration in a sample when viscosity or matrix effects might cause erroneous results.
torch: A series of three concentric tubes, usually manufactured from quartz, in which the ICP is formed.
1 Yueh F-Y, Singh JP, Zhang H. Laser-induced breakdown spectroscopy, elemental analysis. In: Encyclopedia of Analytical Chemistry: Instrumentation and Applications. New York: Wiley; 2000:20662087.
Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 312Pharmacopeial Forum: Volume No. 32(3) Page 836